Growth inhibition of colon cancer cells by transfection of dominant-negative apoptosis signal-regulating kinase-1

  • Authors:
    • Hikaru Kuwamura
    • Kazunari Tominaga
    • Masayuki Shiota
    • Reiko Ashida
    • Takafumi Nakao
    • Eiji Sasaki
    • Toshio Watanabe
    • Yasuhiro Fujiwara
    • Nobuhide Oshitani
    • Kazuhide Higuchi
    • Hidenori Ichijo
    • Tetsuo Arakawa
    • Hiroshi Iwao
  • View Affiliations

  • Published online on: April 1, 2007     https://doi.org/10.3892/or.17.4.781
  • Pages: 781-786
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Abstract

Apoptosis signal-regulating kinase-1 (ASK-1) is an important molecule for the pro-apoptotic signaling. ASK-1 also contributes to the cellular survival for many types of cells. Thus, ASK-1 has a broad range of biological activities depending on the cell type. The present study assessed the role(s) of ASK-1 in colorectal cancer cells (HT-29) by using adenovirus vectors expressing wild-type (WT)-ASK-1 or dominant-negative (DN) mutant of ASK-1 and recombinant adenovirus containing the bacterial β-galactosidase gene (Ad-LacZ), a negative control for Ad-DN-ASK-1. Selective phosphorylation of ASK-1 at Thr 845, a kinase domain site, but not Ser 83 nor 967 sites was induced by serum stimulation in a time-dependent manner. Transfection with Ad-DN-ASK-1 inhibited the serum-induced phosphorylation of p38 mitogen-activated protein kinase, a downstream molecule of ASK-1. Transfection with Ad-DN-ASK-1 diminished the serum-induced cell proliferation in a dose-dependent manner, whereas WT-ASK-1 increased it. Apoptosis assessed by Hoechst staining was induced in the Ad-DN-ASK-1 treated cells. In vivo transfection of Ad-DN-ASK-1 into tumor xenografts of HT-29 cells in nude mice significantly decreased the tumor volume on day 29. Cleaved caspase-3 was found in the tumors of DN-ASK-1 treated mice. We obtained the first evidence that DN-ASK-1 transfection exerted significant antitumor effects on colon cancer mediated by apoptosis.

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April 2007
Volume 17 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kuwamura H, Tominaga K, Shiota M, Ashida R, Nakao T, Sasaki E, Watanabe T, Fujiwara Y, Oshitani N, Higuchi K, Higuchi K, et al: Growth inhibition of colon cancer cells by transfection of dominant-negative apoptosis signal-regulating kinase-1. Oncol Rep 17: 781-786, 2007
APA
Kuwamura, H., Tominaga, K., Shiota, M., Ashida, R., Nakao, T., Sasaki, E. ... Iwao, H. (2007). Growth inhibition of colon cancer cells by transfection of dominant-negative apoptosis signal-regulating kinase-1. Oncology Reports, 17, 781-786. https://doi.org/10.3892/or.17.4.781
MLA
Kuwamura, H., Tominaga, K., Shiota, M., Ashida, R., Nakao, T., Sasaki, E., Watanabe, T., Fujiwara, Y., Oshitani, N., Higuchi, K., Ichijo, H., Arakawa, T., Iwao, H."Growth inhibition of colon cancer cells by transfection of dominant-negative apoptosis signal-regulating kinase-1". Oncology Reports 17.4 (2007): 781-786.
Chicago
Kuwamura, H., Tominaga, K., Shiota, M., Ashida, R., Nakao, T., Sasaki, E., Watanabe, T., Fujiwara, Y., Oshitani, N., Higuchi, K., Ichijo, H., Arakawa, T., Iwao, H."Growth inhibition of colon cancer cells by transfection of dominant-negative apoptosis signal-regulating kinase-1". Oncology Reports 17, no. 4 (2007): 781-786. https://doi.org/10.3892/or.17.4.781